The active metabolite of vitamin D, 1,15-dihydroxycholecalciferol (1,25-(OH)2CC, is a steroid hormone which acts to regulate calcium metabolism in mineralizing tissues. The objective of the proposed research is to investigate the mechanism of Vitamin D action in the avian shell gland as a model system for other mineralizing tissues such as bone. The shell gland is of particular advantage because large amounts of tissue can be obtained for biochemical studies, there are a limited number of cell types, well-characterized differentiation occurs in response to estrogen, and the shell gland is an extremely active mineralizing tissue. These advantages are in direct contrast to the properties of bone, a fact which has hampered the investigation of hormone regulation of bone mineralization. Studies will be carried out to identify and characterize specific shell gland receptor proteins for 1,25-(OH)2CC and to assess the effect of vitamin D on the levels of two shell gland proteins implicated in egg shell formation: calcium binding protein (CaBP) and calcium-stimulated ATPase. These experiments will assess the hypothesis that the shell gland is a target organ for the regulation of calcium transport by vitamin D. In addition, the effect of estrogen-induced growth and differentiation on vitamin D receptor, CaBP and Ca ion-stimulated ATPase levels will be determined in order to provide information on the development of mineralizing tissues. Finally, estrogen withdrawal from estrogen-treated immature chicks results in shell gland regression, a process which may relate to the events occurring in human bone after menopause and during aging. Therefore, studies will be carried out to determine the effects of estrogen withdrawal on shell gland vitamin D receptors and the variation of CaBP and Ca ion-stimulated ATPase levels in response to vitamin D administration. These experiments will test the validity of the degenerating shell gland as a model system for postmenopausal osteoporosis.